scholarly journals Neuropharmacological characteristics of antidepressant action of a new 3-substituted thietane-1,1-dioxide derivative

2021 ◽  
Vol 7 (3) ◽  
pp. 63-71
Author(s):  
Irina L. Nikitina ◽  
Gulnara G. Gaisina
Keyword(s):  
Mechanism Of Action ◽  
Adrenergic Receptors ◽  
Depressive Disorders ◽  
Induced Hypothermia ◽  
Male Mice ◽  
Single Intraperitoneal Injection ◽  
Dose Dependent ◽  
Positive Properties ◽  
Low Rate ◽  
Antidepressant Action

Introduction: Due to severe burden of depressive disorders and a low rate of remission in patients receiving antidepressant therapy, there is an urgent need for developing novel agents with antidepressant action and a fundamentally new mechanism of action. 3-ethoxythietane-1,1-dioxide (N-199/1) is a new molecule that showed significant antidepressant properties when administered intraperitoneally once or repeatedly. The aim of the present study was to investigate the mechanism of action of N-199/1, using reserpine test. Materials and methods: N-199/1 (2 mg/kg and 4.86 mg/kg) and the reference drugs (imipramine and fluoxetine) were administered once intraperitoneally to outbred male mice 4 h (Experiment 1) and 18 h (Experiment 2) after a single intraperitoneal injection of reserpine (2.5 mg/kg). The severity of reserpine-induced symptoms (hypothermia, ptosis and akinesia) was assessed. Results and discussion: N-199/1 potentiated reserpine-induced hypothermia at both doses and reduced ptosis at a dose of 2 mg/kg when administered 4 h after reserpine. N-199/1 increased the duration of reserpine akinesia at a dose of 2 mg/kg when administered 18 h after reserpine and at a dose of 4.86 mg/kg when administered 4 h after reserpine. The effect of N-199/1 resembled the effect of fluoxetine and was dose-dependent. Conclusion: Based on the results obtained, it can be assumed that the antidepressant action of N-199/1 is due to its serotonin-positive properties, and probably the blockade of serotonin 5HT2A/2C receptors and/or α2-adrenergic receptors. The effect of N-199/1 is dose-dependent and resembles the effect of fluoxetine. Graphical abstract:

scholarly journals The Ketamine Antidepressant Story: New Insights

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5777
Author(s):  
Tahani K. Alshammari
Keyword(s):  
Molecular Mechanisms ◽  
Depressive Disorders ◽  
Major Depressive ◽  
Aspartate Receptor ◽  
Antidepressant Effects ◽  
Major Depressive Disorders ◽  
Resistant Depression ◽  
Voltage Gated Channels ◽  
Dose Dependent ◽  
Antidepressant Action

Ketamine is a versatile agent primarily utilized as a dissociative anesthetic, which acts by blocking the excitatory receptor N-methyl-d-aspartate receptor (NMDA). It functions to inhibit the current of both Na+ and K+ voltage-gated channels, thus preventing serotonin and dopamine reuptake. Studies have indicated that administering a single subanesthetic dose of ketamine relieves depression rapidly and that the effect is sustained. For decades antidepressant agents were based on the monoamine theory. Although ketamine may not be the golden antidepressant, it has opened new avenues toward mechanisms involved in the pathology of treatment-resistant depression and achieving rapid antidepressant effects. Thus, preclinical studies focusing on deciphering the molecular mechanisms involved in the antidepressant action of ketamine will assist in the development of a new antidepressant. This review was conducted to elucidate the emerging pathways that can explain the complex dose-dependent mechanisms achieved by administering ketamine to treat major depressive disorders. Special attention was paid to reviewing the literature on hydroxynorketamines, which are ketamine metabolites that have recently attracted attention in the context of depression.

Biological and Phytochemical Screening of Tephrosia purpurea extract on Chemically Induced Hepatocellular Carcinoma with Reference to Biochemical Parameters

2019 ◽  
Vol 10 (02) ◽  
Author(s):  
Irfan Aziz ◽  
Birendra Shrivastava ◽  
Chandana Venkateswara Rao ◽  
Sadath Ali
Keyword(s):  
Free Radicals ◽  
Ethanolic Extract ◽  
Hepatoprotective Activity ◽  
Control Group ◽  
Marker Enzymes ◽  
Tephrosia Purpurea ◽  
Single Intraperitoneal Injection ◽  
Chemically Induced ◽  
Ccl4 Treatment ◽  
Dose Dependent

Tephrosia purpurea possesses hepatoprotective activity as evidenced by the significant and dose dependent restoring the activities of entire liver cancer marker enzymes, diminution in tumor incidence, decrease in lipid peroxidation (LPO) and increase in the level of antioxidant enzymes (GSH, CAT, SOD, GPx and GST) through scavenging of free radicals, or by enhancing the activity of antioxidant, which then detoxify free radicals. These factors protect cells from ROS damage in NDEA and CCl4-induced hepatocarcinogenesis. Histopathological observations of liver tissues too correlated with the biochemical observations. Thus, present investigation suggested that the Tephrosia purpurea would exert a chemoprotective effect by reversing the oxidant-antioxidant imbalance during hepatocarcinogenesis induced by NDEA and CCl4. Besides Tephrosia purpurea is very much effective in preventing NDEA-induced multistage hepatocarcinogenesis possibly through antioxidant and antigenotoxic nature, which was confirmed by various liver injury and biochemical tumour markers enzymes. The hepatoprotective activity of aTephrosia purpurea of 50 % ethanolic extract was studied using rats. The animals received a single intraperitoneal injection of N-nitrosodiethylamine 200mg/kg body wt followed by subcutaneous injection of CCl4 in a dose of 3 ml/kg body wt.Tephrosia purpureaextract dose dependently and significantly the increase in serum hepatic enzyme levels after NDEAand CCl4 treatment compared to the toxin control group. The results of this study confirmed the antioxidant and hepatoprotective activity of the Tephrosia purpurea extract against carbon tetrachlorideand N-nitrosodiethylamine induced hepatotoxicity in rats.

The effect of deer antler from East Kalimantan to increase trabecular bone density and calcium levels in serum on osteoporotic mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Retno Widyowati ◽  
Suciati Suciati ◽  
Dewi Melani Haryadi ◽  
Hsin-I Chang ◽  
IPG Ngurah Suryawan ◽  
...  
Keyword(s):  
Bone Density ◽  
Trabecular Bone ◽  
Aqueous Extract ◽  
Dependent Manner ◽  
Aqueous Extracts ◽  
Trabecular Bone Density ◽  
Male Mice ◽  
Deer Antler ◽  
East Kalimantan ◽  
Dose Dependent

Abstract Objectives Glucocorticoid-induced osteoporosis (dexamethasone) is a primary cause of secondary osteoporosis by the decreasing formation and increasing resorption activities. Previously, the in vitro study showed that 70% ethanol and aqueous extract of deer antler have increased alkaline phosphatase in osteoblast cell that known as marker of bone formation. The mind of this study is to analyze the effect of deer antlers in increasing the bone trabecular density of osteoporosis-induced male mice. Methods This study used a post-test control group design. A total of 54 healthy male mice were randomly divided to nine groups, i.e., healthy control, osteoporotic, positive control, 70% ethanol (4, 8, and 12 mg/kg BW), and aqueous extracts (4, 8, and 12 mg/kg BW) of deer antler groups. All of the interventions were given 1 mL of test sample for 4 weeks orally. The bone densities were determined using histomorphometry by Image J and Adobe Photoshop. The statistical data were performed using SPSS 23 and statistical significance was set at p<0.05. Results The results showed that alendronate group, 70% ethanol, and aqueous extract groups increased bone density and calcium levels in serum (p<0.05) compared to osteoporotic group in dose dependent manner. It indicated that 70% ethanol and aqueous extract of deer antler stimulating bone turnover and aqueous extract showed the highest. Conclusions Dexamethasone induction for 4 weeks caused osteoporotic mice and the administration of 70% ethanol and aqueous extracts of deer antler from East Kalimantan increased trabecular bone density and calcium levels in dose dependent manner.

scholarly journals Preliminary Pharmacogenetic Study to Explore Putative Dopaminergic Mechanisms of Antidepressant Action

2021 ◽  
Vol 11 (8) ◽  
pp. 731
Author(s):  
Taichi Ochi ◽  
Natalya M. Vyalova ◽  
Innokentiy S. Losenkov ◽  
Diana Z. Paderina ◽  
Ivan V. Pozhidaev ◽  
...  
Keyword(s):  
Depressive Disorders ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Sufficient Evidence ◽  
Therapeutic Effects ◽  
Pharmacogenetic Study ◽  
Dopaminergic Mechanisms ◽  
Major Depressive Disorders ◽  
Related Proteins ◽  
Antidepressant Action

Background: There is sufficient evidence that interference of dopaminergic neurotransmission contributes to the therapeutic effects of antidepressants in unipolar and bipolar depression. Methods: Hamilton depression rating scale (HAMD 17) scores of 163 at least moderately ill patients with major depressive disorders were used to establish treatment response. HAMD 17 score status was measured before initiation, after two weeks, and after four weeks of treatment with various antidepressants. The possible association between response and genotype in a total of 14 variants of dopamine neurotransmission-related proteins was investigated. Results: DRD4 rs11246226 CA heterozygous patients were found with a greater improvement of HAMD 17 score when compared to homozygous C patients during 0–2 weeks and 0–4 weeks. Patients with MAOB rs1799836 heterozygous GA and homozygous A also demonstrated improved scores during 2–4 weeks and 0–4 weeks. Conclusions: The results are preliminary due to the limited population size and the small number of variants. Further research into the involvement of habenular dopamine D4 receptors in the antidepressant response is desirable.

scholarly journals Reevaluation of Hepatocellular Neoplasms in CD-1 Mice from a 2-year Oral Carcinogenicity Study with Permethrin

2018 ◽  
Vol 47 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Erin M. Quist ◽  
Gary A. Boorman ◽  
John M. Cullen ◽  
Robert R. Maronpot ◽  
Amera K. Remick ◽  
...  
Keyword(s):  
Chronic Toxicity ◽  
Expert Panel ◽  
Biological Significance ◽  
Male Mice ◽  
Male And Female ◽  
Female Mice ◽  
Carcinogenicity Study ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
The Continuum

A 24-month oral carcinogenicity study of permethrin was conducted by feeding male and female CD-1 mice diets containing concentrations of 0, 20, 500, and 2,000 ppm of permethrin (males) or 0, 20, 2,500, and 5,000 ppm of permethrin (females). After approximately two years on study, surviving mice were sacrificed for the evaluation of chronic toxicity and/or carcinogenicity. An expert panel of pathologists was convened as a Pathology Working Group (PWG) to review coded liver histology sections from male and female mice and to classify all liver neoplasms according to current nomenclature and diagnostic criteria guidelines. The PWG results indicate that permethrin induced a significant dose-dependent increase in the incidence of hepatocellular neoplasms in treated female mice ( p < .01) as well as a nonstatistically significant increase in the incidence of hepatocellular tumors in treated male mice. Given the continuum of the diagnoses of adenoma and carcinoma, and the difficulty in distinguishing some of the lesions, it is appropriate to consider only the combined incidences of hepatocellular tumors (adenoma and/or carcinoma) for biological significance and risk assessment.

Alpha 1b-adrenoceptor-mediated stimulation of Na-K pump current in adult rat ventricular myocytes

1993 ◽  
Vol 264 (4) ◽  
pp. H1315-H1318 ◽  
Author(s):  
A. P. Williamson ◽  
R. H. Kennedy ◽  
E. Seifen ◽  
J. P. Lindemann ◽  
J. R. Stimers
Keyword(s):  
Adrenergic Receptors ◽  
Ventricular Myocytes ◽  
Pump Current ◽  
Peak Effect ◽  
Patch Clamp Technique ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
Whole Cell Patch Clamp ◽  
Dose Dependent ◽  
Stimulation Of

The purpose of this study was to determine if myocardial alpha 1a-and/or alpha 1b-adrenoceptors are involved in the increase in Na-K pump current (Ip) elicited by alpha 1-adrenergic agonists. Single rat ventricular myocytes were isolated by enzymatic disaggregation. The whole cell patch-clamp technique was used to examine dose-dependent effects of phenylephrine (PE) on holding current (Ih) and to determine whether observed actions were mediated via alpha 1a-or alpha 1b-adrenergic receptors. To minimize the contribution of transsar-colemmal currents other than Ip to Ih, membrane voltage was held constant -40 mV, and cells were maintained in a Ca-free perfusate containing 1 mM Ba and 0.1 mM Cd. All experiments were conducted in the presence of 3 microM nadolol. PE elicited dose-dependent increases in Ih, with a peak effect of 0.57 +/- 0.03 pA/pF observed at 30 microM. The response to PE was dose dependently inhibited by prazosin and chloroethylclonidine and was totally eliminated by 1 mM ouabain. When used at doses selective for the alpha 1a-subtype, WB4101 failed to significantly antagonize the action of PE. These data suggest that the observed alpha 1-adrenoceptor-mediated increase in Ih in isolated rat ventricular myocytes is the result of an increase in Ip effected via stimulation of alpha 1b-adrenergic receptors.

scholarly journals Therapeutic effect and mechanism of action of quercetin in a rat model of osteoarthritis

2019 ◽  
Vol 48 (3) ◽  
pp. 030006051987346 ◽  
Author(s):  
Jun Zhang ◽  
Jing Yin ◽  
Daohong Zhao ◽  
Chaoran Wang ◽  
Yuhao Zhang ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Mechanism Of Action ◽  
Rat Model ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Tnf Α ◽  
Dose Dependent ◽  
Light Chain Enhancer ◽  
Necrosis Factor

Objective To study the therapeutic effect and mechanism of action of quercetin in a rat model of osteoarthritis (OA). Methods The OA rat model was established by intra-articular injection of papain. Changes in knee diameter, toe volume and histopathology were measured. Levels of interleukin (IL)-β and tumor necrosis factor (TNF)-α were assessed by ELISA. Relative expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was evaluated by western blotting. Results Compared with rats treated with papain alone, changes in knee diameter, toe volume and Makin' s score were less apparent in OA rats treated with quercetin. Levels of serum IL-1β and TNF-α were also reduced in quercetin-treated OA rats. Expression of TLR-4 and NF-κB was significantly suppressed in a dose-dependent manner in quercetin-treated OA rats. Conclusion Quercetin exhibited a therapeutic effect in OA rats, which may be related to inhibition of IL-1β and TNF-α production via the TLR-4/NF-κB pathway.

scholarly journals Inhibitory Effect of r-Hirudin Variant III on Streptozotocin-Induced Diabetic Cataracts in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaojian Gong ◽  
Qiuyan Zhang ◽  
Shuhua Tan
Keyword(s):  
Inhibitory Effect ◽  
Morphological Observation ◽  
Eye Lens ◽  
Dependent Manner ◽  
Slit Lamp ◽  
Cataract Formation ◽  
Sd Rats ◽  
Single Intraperitoneal Injection ◽  
Dose Dependent

Thein vivoinhibitory effect of r-hirudin variant III (rHV3) on streptozotocin (STZ)-induced diabetic cataracts in rats was investigated. SD-rats were firstly made diabetic by a single intraperitoneal injection of 2% (W/V) STZ (65 mg/kg). Two weeks later, cataract formation was examined by slit lamp microscope, and the cataracted animals were randomly grouped. The animals in the treated groups received rHV3 drops administration to the eyes with various doses. After 4 weeks treatment, the animals were sacrificed to evaluate the biochemical changes of aldose reductase (AR), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels in the eye lens. Meanwhile, the cataract progression was monitored by slit lamp microscope. As a result, rHV3 drops treatment significantly increased the activities of SOD and GSH-Px in the lens in a dose-dependent manner, whereas AR activity and MDA level in the lens were dramatically decreased. Also, the morphological observation further confirmed the inhibition of the development of STZ-induced diabetic cataracts by the rHV3 drops treatment. Thus, our data suggest that rHV3 drops are pharmacologically effective for the protection against STZ-induced diabetic cataracts in rats.

scholarly journals Selenium and manganese in depression – preclinical and clinical studies

2017 ◽  
Vol 30 (3) ◽  
pp. 151-155
Author(s):  
Karolina Slawinska ◽  
Gabriela Bielecka ◽  
Karol Iwaniak ◽  
Sylwia Wosko ◽  
Ewa Poleszak
Keyword(s):  
Clinical Studies ◽  
Depressive Disorders ◽  
Economic Loss ◽  
Essential Elements ◽  
World Health ◽  
Neurotransmitter System ◽  
Health Organization ◽  
Preclinical And Clinical Studies ◽  
The Relationship ◽  
Antidepressant Action

AbstractAccording to the World Health Organization estimates, approximately 10% of the world’s population is affected by depressive disorders. Furthermore, even in high-income countries, many people with depression are not treated, which can lead to serious health consequences and a global economic loss. Unfortunately, the current pharmacotherapy of depressive disorders is characterized by unsatisfactory efficacy and the therapeutic effect is accompanied by many side effects. For this reason, there is still ongoing worldwide research to find new antidepressant therapies. In recent years, many data have been shown that essential elements demonstrate the antidepressant action and increase the effect of antidepressants. In this paper we present the results from the preclinical and clinical studies published over the years which show the involvement of selenium and manganese in depressive disorders. In this article, the relationship between the amount of these microelements in a diet and depression is reviewed and what's more, the association among these elements in different biomaterial and their relations to depressive symptoms is presented. Additionally, we discuss the possible influence of selenium and manganese on modulating neurotransmitter system involved in depression.

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